An influential mentor, Southard guided several well-known figures in medicine and psychology. He worked with neuropathologist Myrtelle Canavan early in her career, and used his influence to obtain a promotion for her in Boston. Southard introduced Karl Menninger to psychiatry, and Menninger later helped establish the foundation which bears his family name. Comparative psychologist Robert Yerkes called Southard "my master of psychopathology."
Southard was married to physician and Wellesley College professor Mabel Fletcher Austin, and they had three children. His interest in chess continued throughout his life, and he enjoyed intellectual gatherings at the home of art collector and friend Walter Arensberg. At the age of 43, Southard died of pneumonia in 1920 during a trip to New York City to deliver lectures to two medical societies.